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1.
Cureus ; 15(4): e38027, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37228528

ABSTRACT

Introduction Colonoscopic polypectomy is a well-established screening and surveillance modality for malignant colorectal polyps. Following the detection of a malignant polyp, patients are either put on endoscopic surveillance or planned for a surgical procedure. We studied the outcome of colonoscopic excision of malignant polyps and their recurrence rates. Methods We performed a retrospective analysis over a period of five years (2015-2019) of patients who underwent colonoscopy and resection of malignant polyps. Size of polyp, follow-up with tumour markers, CT scan, and biopsy were considered individually for pedunculate and sessile polyps. We analysed the percentage of patients who underwent surgical resection, the percentage of patients who were managed conservatively, and the percentage of recurrence post-excision of malignant polyps. Results A total of 44 patients were included in the study. Of the 44 malignant polyps, most were present in the sigmoid colon at 43% (n=19), with the rectum containing 41% (n=18). The ascending colon accounted for 4.5% (n=2), transverse colonic polyps were 7% (n=3), and the descending colon polyps were 4.5% (n=2). Pedunculated polyps made up 55% (n=24). These were Level 1-3 based on Haggits classification; 14 were Haggits Level 1, eight were Haggits Level 2, and two were Haggits Level 3. The rest were sessile polyps making up 45% (n=20). Based on the Kikuchi classification, these were predominantly SM1 (n=12) and SM2 (n=8). Out of 44 cases, 11% (n=5) underwent surgical resection on follow-up in the form of bowel resection. This included three right hemicolectomies, one sigmoid colectomy, and one low anterior resection. Seven per cent (n=3) underwent endoscopic resection as trans-anal endoscopic mucosal resection (TEMS) and 82% (n=36) of the remaining cases were managed with regular follow-up and surveillance. Conclusions Colonoscopic polypectomy offers excellent benefits in detecting colorectal cancer and treating pre-malignant polyps. Colonoscopic polypectomy provides excellent benefits in colorectal cancer (CRC) detection and treatment of malignant polyps. However, it remains to be seen if post-polypectomy surveillance for low-risk polyp cancers would require a change in surveillance.

2.
Cell ; 185(13): 2354-2369.e17, 2022 06 23.
Article in English | MEDLINE | ID: mdl-35568036

ABSTRACT

Interferons (IFNs) induce an antimicrobial state, protecting tissues from infection. Many viruses inhibit IFN signaling, but whether bacterial pathogens evade IFN responses remains unclear. Here, we demonstrate that the Shigella OspC family of type-III-secreted effectors blocks IFN signaling independently of its cell death inhibitory activity. Rather, IFN inhibition was mediated by the binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II and downstream JAK/STAT signaling. The growth of Shigella lacking OspC1 and OspC3 was attenuated in epithelial cells and in a murine model of infection. This phenotype was rescued in both models by the depletion of IFN receptors. OspC homologs conserved in additional pathogens not only bound CaM but also inhibited IFN, suggesting a widespread virulence strategy. These findings reveal a conserved but previously undescribed molecular mechanism of IFN inhibition and demonstrate the critical role of Ca2+ and IFN targeting in bacterial pathogenesis.


Subject(s)
Interferons , Virulence Factors , Animals , Antiviral Agents , Calcium Signaling , Epithelial Cells/metabolism , Interferons/metabolism , Mice , Virulence Factors/metabolism
3.
J Psychopharmacol ; 30(12): 1220-1229, 2016 12.
Article in English | MEDLINE | ID: mdl-27856684

ABSTRACT

Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s. They are relatively safe when used in medically controlled environments, with no reported risk of dependence. Here, we present a systematic review of published clinical treatment studies using psychedelics in patients with broadly defined UMD, and consider their place in psychiatry. Whilst all of the included studies have methodological shortcomings, of 423 individuals in 19 studies, 335 (79.2%) showed clinician-judged improvement after treatment with psychedelics. A recently completed pilot study in the UK favours the use of psilocybin with psychological support in treatment resistant depressive disorder. The evidence overall strongly suggests that psychedelics should be re-examined in modern clinical trials for their use in unipolar mood disorders and other non-psychotic mental health conditions.


Subject(s)
Hallucinogens/therapeutic use , Mood Disorders/drug therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Humans , Lysergic Acid Diethylamide/therapeutic use , Pilot Projects , Psilocybin/therapeutic use , Treatment Outcome
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